I will continue ongoing studies designed to characterize the mechanism by which the Epstein-Barr nuclear antigen 1 (EBNA-1) protein of Epstein-Barr virus (EBV) facilitates the stable replication of plasmids that bear oriP, EBV's plasmid origin of replication. Together my post-doctoral mentor, Dr. Bill Sugden, and I have demonstrated that oriP-plasmids are synthesized directly by the cell, and that EBNA-1 functions post- synthetically to stabilize oriP-plasmids. Our work also demonstrates that human cells can actively eliminate extra- chromosomal DNAs. This application experimentally addresses the process by which human cells eliminate plasmids, by defining when it occurs in the cell-cycle, and understanding the mechanism by which those viruses that maintain their genomes as plasmids in human cells overcome it. It also experimentally addresses the mechanism by which oriP-plasmids are stabilized so that they can be partitioned faithfully to daughter cells, and the contributions of EBNA-1 to these processes.